A "bottom-up" approach to aetiological research in autism spectrum disorders.

Autism spectrum disorders (ASD) are currently diagnosed in the presence of impairments in social interaction and communication, and a restricted range of activities and interests. However, there is considerable variability in the behaviors of different individuals with an ASD diagnosis. The heterogeneity spans the entire range of IQ and language abilities, as well as other behavioral, communicative, and social functions. While any psychiatric condition is likely to incorporate a degree of heterogeneity, the variability in the nature and severity of behaviors observed in ASD is thought to exceed that of other disorders. The current paper aims to provide a model for future research into ASD subgroups. In doing so, we examined whether two proposed risk factors - low birth weight (LBW), and in utero exposure to selective serotonin reuptake inhibitors (SSRIs) - are associated with greater behavioral homogeneity. Using data from the Western Australian Autism Biological Registry, this study found that LBW and maternal SSRI use during pregnancy were associated with greater sleep disturbances and a greater number of gastrointestinal complaints in children with ASD, respectively. The findings from this "proof of principle" paper provide support for this "bottom-up" approach as a feasible method for creating homogenous groups.

Intravenous secretin for autism spectrum disorders (ASD).

BACKGROUND: In 1998 secretin, a gastrointestinal hormone, was suggested as an effective treatment for autism spectrum disorders (ASD) based on anecdotal evidence. OBJECTIVES: To assess whether intravenous secretin improves the core features of ASD, other aspects of behaviour or function such as self-injurious behaviour, and the quality of life of affected individuals and their carers. We also assessed whether secretin causes harm. This is an updated version of our review of this topic originally published in 2005. SEARCH METHODS: We searched CENTRAL (2010 Issue 1), MEDLINE (1950 to January 2010) , EMBASE (1980 to 2010 Week 2), PsycINFO (1806 to 2010 Week 2), CINAHL (1938 to January 2010), ERIC (1966 to January 2010), Sociological Abstracts (1952 to January 2010). Sociofile and HealthStar were searched in March 2005 when this review was first published, but were not available for this update. Records were limited to studies published since 1998 as this is when secretin was first proposed as a possible treatment for ASD. We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies. SELECTION CRITERIA: Randomised controlled trials of intravenous secretin compared to a placebo treatment in children or adults diagnosed with ASD, where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS: Sixteen studies met the inclusion criteria but for two of these, conducted by Repligen, the only available multisite data were reported in press releases. All outcome data from the other 14 trials were continuous. Where trials used cross-over designs, we conducted analysis on results from the first treatment phase. Where mean change from baseline was reported, we used this in preference to post-treatment scores for meta-analyses or forest plots. Meta-analysis was able to be attempted for only one outcome (Childhood Autism Rating Scale). Insufficient data were available to conduct sensitivity or subgroup analyses to assess the impact of study quality, clinical differences in the intervention or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms. MAIN RESULTS: Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD. AUTHORS' CONCLUSIONS: There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.

No association between early gastrointestinal problems and autistic-like traits in the general population.

AIM: The aim of this study was to determine whether gastrointestinal problems in early childhood relate to autistic-like traits in a general population sample. METHOD: The parents of 804 children (442 females; 362 males) reported at 1-, 2-, 3-, and 5-year follow-ups whether their child had been taken to a hospital, general practitioner, or health clinic for any of five gastrointestinal symptoms: (1) constipation; (2) diarrhoea; (3) abdominal bloating, discomfort, or irritability; (4) gastro-oesophageal reflux or vomiting; and (5) feeding issues or food selectivity. Parents also reported whether their child had received the measles, mumps, and rubella vaccination. Autistic-like traits were measured when the children had reached early adulthood (mean age 19 y 7 mo; SD 0.63 y) using a self-report questionnaire, the Autism Spectrum Quotient (AQ). RESULTS: There was no statistically significant difference in AQ scores between those who had (n=133) and those who had not (n=671) experienced early gastrointestinal symptoms. χ(2) analyses revealed that the children with early gastrointestinal problems were no more likely to be represented in the upper quintile of scores on any of the AQ scales. The measles, mumps, and rubella vaccination was unrelated to gastrointestinal symptoms or AQ scores. INTERPRETATION: Parent-reported gastrointestinal problems in early childhood are unrelated to self-reported autistic-like traits in the general population.

Digestive enzyme supplementation for autism spectrum disorders: a double-blind randomized controlled trial.

To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating Scales, Additional Rating Scales of other symptoms by parents and therapists, and monthly completion of the Rescorla Language Development Survey. Compared with placebo, treatment with enzyme was not associated with clinically significant improvement in behaviour, food variety, gastrointestinal symptoms, sleep quality, engagement with therapist, or the Language Development Survey Vocabulary or Sentence Complexity Scores. A small statistically significant improvement on enzyme therapy was seen for the food variety scores. No clinically significant effect improvement of autism symptoms with enzyme use was shown with this trial, however, possible effects on improvement in food variety warrants further detailed investigation.

The prevalence of autism in Australia. Can it be established from existing data?

AIM: To assess whether existing data collection mechanisms can provide accurate and sufficient information about the prevalence of autism in Australia. METHODS: Summary data about the number of children aged 0-16 years known to have an autism spectrum disorder (ASD) were gathered from State and Territory health, disability, education sources and autism associations. Summary data were also provided by national sources. Initial contact was made by letter, and follow-up was undertaken by telephone or email. RESULTS: For the years 2003-2004, the estimated prevalence of autism for 6- to 12-year-olds ranged from 9.6 to 40.8/10 000 for the State and Territory data, and from 12.1 to 35.7/10 000 for the national data. There was a similar variation in prevalence estimates for children aged 0-5 and 13-16 years. There was also a variation in prevalence estimates between age groups. CONCLUSION: Inconsistencies in autism prevalence estimates calculated from existing data sources suggest that further efforts are needed to ensure the collection of reliable information about the prevalence of ASD for national, State and Territory use. Existing data systems need to be improved or additional data systems need to be developed to ensure the collection of reliable information. Reliable and consistent ASD prevalence data would ensure that services are being provided to those who need them and would enhance the opportunities to undertake meaningful population-based research.